A look at the different aging processes and their effects on our health.
Age is complex and cannot be expressed in a single number. Two people of the same age can be very different – one healthy, the other sick or suffering from chronic conditions. Even within the human body, age cannot be uniform. Some parts of the body may be healthy and still functioning well, while other organs are already on the verge of failure. Experts say that the ovaries age so quickly that women in their thirties are already geriatric.
A good comparison is between the human body and a car—both need careful maintenance. If a car’s paintwork is not scratched, it can last for decades. An engine can run for a lifetime if it is regularly well maintained. Brake pads wear out very quickly and tires should be replaced every few years, but you may not need a new clutch until middle age. The service booklet and dashboard indicators remind you when the next service is due.
In the future, similar to cars, there could also be a “control dashboard” for human health that provides us with important health data and maintenance schedules. Experts are working to develop such technologies to better monitor and maintain our health.
Clocks for measuring the aging process
When scientist Steve Horvath introduced his so-called Horvath clock, it was a step in this direction. The clock is an instrument for measuring biological aging based on epigenetics, i.e., the changing methylation patterns and other types of DNA modifications that change with age. The concept of his clock is based on the fact that DNA methylation patterns change with age. These epigenetic patterns correlate with the aging process and can serve as biomarkers for estimating biological age—in other words, a better measure of how fast we are aging than chronological age.
Since Horvath introduced the first multisystem clock in 2013, a race has begun to find more efficient methods for quantifying the speed and effects of aging on the human body. A study from 2022 used several biomarkers to demonstrate that different parts of the human body age at different rates at the cellular level. A study of healthy adults showed that the turnover rates of certain human cell types, from which cell lifespan can be derived, range from 2 days for one type of white blood cell to 90 years for nerve cells.
Scientists disagree on the best way to measure the biological aging of organs. And despite ongoing research, there is no published, validated, system-specific epigenetic clock. A research group at the University of Melbourne has now developed a new type of biological clock for aging that is not based on epigenetic measurements.
A new way to fight disease?
“The aging of one body system, one organ system, can selectively have a strong influence on the aging of other systems,” says Andrew Zalesky, a neuroscientist at the University of Melbourne. He and a team of scientists have taken this system-oriented measurement of biological age one step further in a study recently published in Nature Medicine. By mapping the selective effects of organs aging at different rates on each other, they created a new way to quantify and potentially combat age-related risk for chronic diseases.
The researchers also found links between the rate of organ-specific aging and lifestyle and demographic factors such as proximity to green spaces, which tend to be associated with “younger” lungs. They also found causal links between organ-specific aging rates. For example, lung aging can lead to a higher rate of heart aging, which in turn can affect the aging rate of other body systems.
Instead of relying on epigenetic aging clocks to measure biological age, the Melbourne scientists derived their “clock” from the UK Biobank, an extensive dataset that has collected genetic and health data from 500,000 people since 2006. In their latest study, the scientists developed a new measure of biological age based on data from brain scans and physiological phenotypes, or characteristics. Using data from healthy adults, they trained machine learning models to predict the age of different parts of the body. By comparing this age with chronological age, the model was able to determine whether, for example, the heart, lungs, or kidneys were older or younger than typical for a given age. This gap was used to derive organ-specific methods for measuring biological age in seven body systems and three brain systems.
For every year that the heart ages biologically, the brain age increases by 27 days.
For example, the researchers found correlations between the aging of the heart and the brain. For every year that the heart ages biologically, the brain age increases by 27 days. The researchers also found correlations between the biological age of various systems and 16 chronic diseases, including osteoarthritis, diabetes, and cancer. While these correlations do not show that a particular disease or lifestyle factor causes organ aging or vice versa, they could be useful in deciphering the complex interactions between these body systems.
The real challenge is to move from a fragmented approach to healthcare—one doctor per organ—to redefining health as a dynamic network of interactions between tissues and organ systems. This means that doctors could focus on specific organs that are aging faster than the surrounding systems, and thus potentially slow down the aging process or halt disease. A better understanding of variations in biological age could also help doctors develop therapies for people based on their individual risk factors.
To stick with the car analogy, as the car ages, everything is subject to wear and tear. When does the exhaust or other critical part need to be replaced if there are signs that something is about to go wrong? An accurate and affordable biological aging test is the ace up the sleeve of the mechanic who recognizes that the air-fuel mixture is off before you even notice a strange smell. Fixing this problem would reduce fuel consumption, make the car run more smoothly, and prevent engine wear. Without a good mechanic (or an accurate, affordable aging clock), we may not notice that something is wrong until it is too late or too expensive to fix. But which aging measurement, which “mechanic,” can you really trust?
References
- Nie, C., Li, Y., Li, R., Yan, Y., Zhang, D., Li, T., Li, Z., Sun, Y., Zhen, H., Ding, J., Wan, Z., Gong, J., Shi, Y., Huang, Z., Wu, Y., Cai, K., Zong, Y., Wang, Z., Wang, R., . . . Xu, X. (2022). Distinct biological ages of organs and systems identified from a multi-omics study. Cell Reports, 38(10), 110459. https://doi.org/10.1016/j.celrep.2022.110459
- Seim, I., Ma, S. & Gladyshev, V. N. (2016). Gene expression signatures of human cell and tissue longevity. Research Gate, 2(1). https://doi.org/10.1038/npjamd.2016.14
- Tian, Y. E., Cropley, V., Maier, A. B., Lautenschlager, N. T., Breakspear, M. & Zalesky, A. (2023). Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nature Medicine, 29(5), 1221–1231. https://doi.org/10.1038/s41591-023-02296-6